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Published on: May 29, 2015
Immunohistochemical detection of the 150-kDa oxygen-regulated protein in bladder cancer
1Department of Urology and Third Department of Anatomy, Kanazawa University School of Medicine, Kanazawa, Japan.
Objective:
To investigate the relationship between the expression of the 150-kDa oxygen-regulated protein (ORP150, which functions as a molecular chaperone in the endoplasmic reticulum for the folding and trafficking of newly synthesized proteins) and the aggressiveness of bladder cancer, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), as the former is a secreting protein through the endoplasmic reticulum and the latter are closely involved in tumour invasion.
Materials And Methods:
Thirty-nine cystectomy specimens, comprising 12 superficial (pT1) and 27 invasive (pT2-pT4) tumours, were immunohistochemically analysed using antibodies against ORP150, VEGF, MMP-1, MMP-2 and MMP-9. Staining was scored from 0 to 3, according to the ratio of positively staining cells.
Results:
Staining was positive (score 1-3) for ORP150 in 10 of 12 superficial and 25 (93%) of the invasive tumours, with a significantly higher staining score for stage T4 than stage T1 tumours. The trend was the same for the staining score of MMP-2, and there was a significant correlation between ORP150 and MMP-2 expression.
Conclusions:
The expression of ORP150 was common in bladder cancer, with a tendency for greater expression in higher stages. The significant correlation between ORP150 and MMP-2 expression suggests that ORP150 acts as a molecular chaperone for MMP-2 secretion and thus tumour invasion.
Insights
Oxygen-regulated protein (ORP150) expression increases with bladder cancer stage. ORP150 correlates with matrix metalloproteinase-2 (MMP-2), suggesting a role in tumor invasion.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oxygen-regulated protein (ORP150) acts as a molecular chaperone in the endoplasmic reticulum, crucial for protein folding and trafficking.
- Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are implicated in tumor invasion and metastasis.
- Understanding the role of ORP150 in bladder cancer progression is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the relationship between ORP150 expression and bladder cancer aggressiveness.
- To examine the correlation between ORP150, VEGF, and MMPs (MMP-1, MMP-2, MMP-9) expression in bladder tumors.
- To elucidate the potential role of ORP150 in tumor invasion through its interaction with MMPs.
Main Methods:
- Immunohistochemical analysis of 39 cystectomy specimens (12 superficial pT1, 27 invasive pT2-pT4 tumors).
- Antibodies used: ORP150, VEGF, MMP-1, MMP-2, and MMP-9.
- Staining intensity scored from 0 to 3 based on the proportion of positive cells.
Main Results:
- ORP150 staining was detected in 10/12 superficial and 93% of invasive bladder tumors.
- Higher ORP150 staining scores were observed in advanced T4 stages compared to early T1 stages.
- A significant positive correlation was found between ORP150 and MMP-2 expression levels.
Conclusions:
- ORP150 expression is prevalent in bladder cancer and tends to increase with tumor stage.
- The significant correlation between ORP150 and MMP-2 suggests ORP150 may facilitate MMP-2 secretion.
- This chaperone activity of ORP150 could contribute to bladder tumor invasion and progression.
